Pemphigus, herpes gestationis, bullous pemphigoid and dermatitis herpetiformis are blistering skin diseases all of which are associated with so-called autoimmune phenomena. We have identified and characterized serum and in vivo bound antibodies in these diseases. Our efforts have centered around the mechanisms of tissue destruction, ultrastructure, and ultrastructural localization of antibodies. Gastrointestinal abnormalities, similar to those seen in gluten sensitive enteropathy, occur in dermatitis herpetiformis and are under active study. Immunogenetic considerations with regard to HLA associations and the identification of specific B-lymphocyte antigens have provided tools to study the triggering mechanisms involved in the early stages of an abnormal immune response. Another major effort is the study of the role of Langerhans cells in inflammatory and immunologically mediated reactions. We have also sought the origin of this cell which probably represents the peripheral most limb of the immune response in the skin. Alterations in collagen synthesis in inflammatory disease and identification and functional characterization of alloantigens on epidermal cells are other integral parts of the overall program.